tbuckley/cabot-search huggingface dataset:
Trends in frontline PARP inhibitor maintenance in advanced epithelial ovarian cancer across the United States.
Authors: Erica Huelsmann, Mengying Deng, Elizabeth A. Handorf, Christina Chu, Angela Jain
Journal: Journal of Clinical Oncology (2022)

5581 Background: Advanced epithelial ovarian cancer (AEOC) is the fifth commonest cancer mortality among women in the United States. Despite 80% initial treatment response, most recur within two years and succumb from disease. Prolonging disease free interval with maintenance therapy is of interest. Options include Poly-(ADP) ribose polymerase inhibitors (PARPi’s) and Bevacizumab, an anti-angiogenesis agent; eligibility criteria are based on clinical trials. Here we examine national approach to front line maintenance therapy following treatment in AEOC with focus on PARPi use. Methods: Protocol for data collection was IRB approved and institutional IRB approved. A retrospective, observational cohort study using Flatiron Health electronic health record (EHR)-derived, de-identified database patients diagnosed with AEOC between March 2017-June 2020, following FDA approval of PARPi use in AEOC. Demographics were summarized using descriptive statistics by use of maintenance treatment, and associations were tested using ANOVA and Chi-squared tests. Trends in use and type of maintenance therapy were summarized by year. Time trends assessed by Cochran–Armitage tests. Results: 1196 patients met inclusion criteria: Age&gt;18, Stage III-IV, 90-day gap rule, systemic therapy after diagnosis. Majority were &gt;65, White, Stage III with ECOG 0 at diagnosis. Only 31.6% of patients received maintenance after frontline therapy. Single agent PARPi was most used (12.9%), and Olaparib was most used PARPi (57%). Use of maintenance therapy significantly differed by ECOG value at diagnosis (p=.005), region of practice (p=.003), use of surgery (p=&lt;.001) and extent of debulking (p=.002). Maintenance therapy was used more often when ECOG low at diagnosis, optimal debulking achieved and with treatment in the Southern US. Maintenance therapy significantly increased by year (p=&lt;0.001); highest in 2020 (46.9%). Type of maintenance therapy had a significantly different trend by year with PARPi becoming more common (p=&lt;.001). Conclusions: Despite known high rates of response to maintenance PARPi and increased use over time, less than 50% of patients with AEOC receive this regimen. Reasons for low adoption of maintenance PARPi in this population with poor prognosis deserves further investigation. Olaparib, approved for single use in BRCA mutation carriers in the front-line maintenance setting was used more often than Niraparib, approved for all comers. [Table: see text]
National trends in post-launch cancer prescription drug prices and the impact of generic entry, 2014-2020.
Authors: Danielle Rodin, Meredith B. Rosenthal, Claire McGlave, Anushka Bhaskar, C To, Rena M. Conti
Journal: Journal of Clinical Oncology (2022)

6598 Background: The high prices of branded ‘on patent’ cancer prescription drugs and the impact of competition on them is of importance to patients, physicians, payers and policymakers. The objective of this study is to quantify trends in the prices of all currently approved cancer drugs and to evaluate the impact of loss of exclusivity and generic entry on prices using national and contemporaneous data. Methods: Observational study of cancer drug prices from the IQVIA National Sales Perspectives from January 2014 to December 2020. The compound annual growth rate (CAGR) of drug prices was calculated for branded and generic drugs by therapeutic class (chemotherapy, targeted therapy, and supportive therapy). An event study empirical strategy and ordinary least squares regression was used to determine the relationship between the natural logarithm of prices and loss of exclusivity and generic entry. Results: The study cohort included 184 cancer drugs (37% chemotherapy, 51% targeted therapy, and 12% supportive therapy), of which 105 were always branded, 18 were always generic and 18 underwent loss of exclusivity and generic entry during the study period. Prices of branded chemotherapies and targeted therapies increased by 2.24% (0.79% CPI-adjusted) and 2.83% (1.07% CPI-adjusted) annually, whereas generics decreased by 12.63% (-14.14% CPI-adjusted) and 20.15% (-21.57% CPI-adjusted), respectively. Prices of branded supportive therapies decreased by 0.73% (-2.40% CPI-adjusted), while generics increased by 1.28% but decreased with CPI-adjustment (-0.45). Loss of exclusivity and generic entry was associated with statistically significant decreases in generic drug prices, but increases in branded drug prices after CPI-adjustment; these effects are concentrated in chemotherapies and targeted therapies. Conclusions: We found that cancer drug prices increased, after adjusting for inflation, particularly among branded chemotherapies and targeted therapies. Generic entry mitigates these price increases, but only a handful of cancer drugs experienced competition in the study period. Drug prices are key determinants of cancer-related spending, and many cancer patients remain underinsured. Although this data reflects net prices before discounts to providers and pharmacies, patient out-of-pocket costs are based on the list price. Our findings are critical to informing current efforts to improve cancer treatment affordability.
An audit of anaplastic carcinoma of thyroid from a single institution.
Authors: Aditya pavan kumar Kanteti, Joy Ghose, Vijay Maruti Patil, Anup Sunil Tamhankar, George Abraham, Vanita Noronha, Sarbani Laskar, Nandini Sharrel Menon, P. S. Pai, Kumar Prabash
Journal: Journal of Clinical Oncology (2022)

e18084 Background: Anaplastic thyroid carcinoma (ATC) is a rare thyroid malignancy with a dire prognosis, nearly 100% disease specific mortality and a median overall survival of less than 6 months. In view of the limited data from India on anaplastic thyroid cancer we conducted this audit to analyze the treatment pattern, outcomes and factors influencing it. Methods: This is a retrospective analysis of outcomes of patients treated in a single institution between Jan 2008- Dec 2020. Baseline characteristics, treatment received and outcomes among adult patients with ATC were collected. Progression free survival (PFS) and Overall survival (OS) were analyzed. SPSS version 20 and R Studio version 3.1.1 were used for analysis. Results: In this cohort of 134 patients, the median age at diagnosis was 59 years, with 63.4% of them being females. At presentation, 70.9% of them had good performance status (PS 0-1). Only 38.8% received treatment with radical intent (either surgery f.b adjuvant or NACT f.b surgery f.b adjuvant or definitive CTRT) while 61.2% patients received palliative treatment (either palliation alone or palliative chemotherapy or palliative surgery or palliative RT). Predominant pattern of progression was local progression (79.8%). Median PFS and OS of the overall cohort was 58 days and 80 days respectively. PFS and OS was significantly better in patients treated with radical intent vs. palliative intent (116 and 134 days Vs 45 and 50 days; p = 0.00 and 0.00 respectively). Among patients treated with radical intent, OS was significantly better in patients undergoing surgery Vs CTRT (155 Vs 76days; p = 0.03). Among patients treated with upfront surgery, both PFS and OS were better with the addition of adjuvant CTRT/RT Vs no adjuvant (332 and 540 days vs 55 and 91 days; p = 0.00 and 0.003 respectively). Conclusions: ATC is a rare cancer with dismal prognosis. Local therapy with surgery followed adjuvant seems to be associated with the better outcomes. Systemic therapy seems to be a better option for palliation. However the outcomes are far from satisfactory and research is required for development of affordable therapies.
Cost-effectiveness of Olaparib plus Bevacizumab versus Bevacizumab in the maintenance of patients with HRD+ advanced ovarian cancer after response to first-line platinum-based chemotherapy in Spain.
Authors: Jose Alejandro Perez-Fidalgo, Ana Cristina Cercos Lleti, Luis Manso, Antonio Casado Herraez, Pedro Ventayol Bosch, Carla Garí, Miriam Padres Martí, Sergio Cedillo Gomez
Journal: Journal of Clinical Oncology (2022)

e17591 Background: Olaparib, a poly (ADP-ribose) polymerase inhibitor (PARPi), monotherapy as first-line maintenance treatment has shown to be cost-effective in ovarian cancer (OC) patients with BRCA mutations in Spain. Regardless of BRCA status, patients with homologous recombination deficiency positive (HRD+) also benefit from PARPi following first-line platinum-based therapy. PAOLA-1 trial confirmed that adding Olaparib to bevacizumab (BEV) significantly increased progression-free survival (PFS) in OC patients. The aim of this study was to assess the cost-effectiveness of Olaparib plus BEV versus BEV monotherapy for the maintenance treatment of HRD+ advanced OC patients after response to first-line platinum-based therapy plus BEV from Spanish National Health System perspective. Methods: A lifetime partitioned survival model with monthly cycles and four health states (PFS, first progression, second progression, and death) was developed. Long-term survival defined as 60 months was included in the mixed survival model as a landmark to extrapolate PFS from the PAOLA-1 trial. Weibull distribution was selected as the most accurate survival model for PFS extrapolation. Time to second progression, and overall survival (OS) were extrapolated using parametric survival models. Mortality was obtained from the OS and adjusted by Spanish mortality rates. Health state utilities and adverse event (AE) frequencies were obtained from PAOLA-1. An expert panel validated data and assumptions. Direct costs including drug acquisition and administration, follow-up, subsequent therapies, AE, and end-of-life were obtained from local sources. A 3% annual discount rate was applied to costs and outcomes. The incremental cost-effectiveness ratio (ICER) was calculated as cost per quality-adjusted life-years (QALYs) gained. One-way and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of the model. Results: Base-case analysis of Olaparib plus BEV compared with BEV showed an ICER of €24,371 per QALY gained. Discount rates applied to outcomes and the cost of Olaparib generated the most significant changes in the ICER. PSA demonstrated that Olaparib plus BEV had a 49.5% and 90.3% probability of being cost-effective versus BEV at a willingness-to-pay of €25,000 and €60,000 per QALY gained, respectively. Conclusions: Olaparib plus BEV is a cost-effective maintenance therapy compared with BEV for patients with HRD+ advanced OC in Spain.[Table: see text]
The response of PD-1 inhibitor combined with Radiotherapy and GM-CSF(PRaG) with or without IL-2 in microsatellite stable metastatic colorectal cancer: Analysis of pooled data from two phase II trials.
Authors: Jiabao Yang, Wei Zhou, Yifu Ma, Di Su, Yuehong Kong, Meiling Xu, Pengfei Xing, Liyuan Zhang
Journal: Journal of Clinical Oncology (2022)

e15561 Background: Immunotherapy has improved outcomes for metastatic colorectal cancer(mCRC) patients with MSI-H/dMMR but has not been effective in MSS/pMMR tumors, which comprise 95% of mCRC. In metastatic cancers, radiotherapy can be used as a local therapy and a sensitizer to PD-1/PD-L1 inhibitors. The synergistic effects of radiotherapy and PD-1/PD-L1 inhibitors can be reinforced by adding cytokines like granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2(IL-2). Our previous PRaG trial demonstrated that PD-1 inhibitors in combination with radiotherapy and GM-CSF could improve clinical response in patients with advanced refractory solid tumors. We found that mCRC patients with MSS/pMMR could also benefit from the PRaG regimen. Methods: Patients of mCRC with MSS/pMMR were collected from the PRaG trial and PRaG 2.0 trial. A treatment cycle consisted of radiotherapy (5 or 8Gy×2-3f) delivered for one metastatic lesion, PD-1 inhibitor dosing within one week after completion of radiotherapy, GM-CSF 200μg subcutaneous (SC) injection once daily for 14 days(d1-14), or GM-CSF 200μg (d1-7), and then sequentially followed by IL-2 200 million IU SC once daily for 7 days(d8-14). PRaG regimen was repeated every 21 days for at least 2 cycles until no appropriate lesions for irradiation or reached the tolerance dose. Pooled analysis of response rate (ORR), median progression-free survival (PFS), and treatment-related adverse eventswere calculated. Results: With the cutoff date of 31 December 2021, a total of 9 mCRC patients with MSS/pMMR were enrolled. All of the patients completed at least 2 cycles of PRaG therapy and one evaluation. The median follow-up was 7.6 months (95%CI, 3.8, 11.4). The ORR was 22.2%, and the disease control rate(DCR) was 66.7%. The median PFS was 5.6 months (95%CI, 1.5 to 9.7). One patient got complete remission, with PFS over 17months. Treatment-related adverse events (TRAE) occurred in 7 of 9 (77.8%) patients. One patient (11.1%) occurred Grade3 TRAE of renal insufficiency. Conclusions: Our preliminary results suggest that the PRaG regimen could improve clinical outcomes in mCRC patients with MSS/pMMR with acceptable toxicity.
A retrospective analysis of the concordance of diagnosis predicted by cancer type ID test with pathological or clinical diagnosis with incorporation of treatment response data.
Authors: Yiqing Xu, Ajinkya Kulkarni, Chinenye Eze-Raphael, Sudhamshi Toom
Journal: Journal of Clinical Oncology (2022)

e18684 Background: Carcinoma of unknown primary site (CUP) is a clinical conundrum, where there is metastatic cancer in multiple organs, but the original site of the cancer cannot be determined either by clinical information, or by pathological specification. In most scenarios, clinical and pathological information may narrow down to 2 or 3 most likely primaries; while in some cases, the pathological diagnosis and the clinical picture may not be in concordance. Cancer type ID test, using a panel of 92 genes detectable by RT-PCR test, and bio-informative algorithm, may provide independent information on the cancer of origin. Incorporating this result, as well as the treatment information, one may be able to get closer to the true site of origin for CUP cases. Methods: Patients who have had a Cancer type ID test (ID test) performed and had received systemic treatment were eligible for this study. We analyzed the concordance of ID result of major probability (&gt; 90% probability) with pathology diagnosis, the concordance of ID result of minor probability (6% probability or “cannot exclude with &lt; 5% probability” with pathology diagnosis, and the concordance of ID result of major probability with final clinical diagnosis (incorporating treatment response data, tumor next gene sequencing data, and genetic test data). We also divided cases into groups of differentiation between 2-3 possible primaries, or true CUPs (as shown in the table below). Results: 26 patients were identified. There were 9 males and 17 females. The median age was 65 years old (ranger 37-92). The final clinical diagnoses were GI (upper and lower intestinal) (n = 6), pancreatic (n = 3), cervical (n = 2), lung adeno (n = 2), lung carcinoid (n = 1), sarcoma (n = 1), GYN (n = 2), Head neck (n = 1) and breast (n = 1). 7 cases remained as CUP. Conclusions: Cancer type ID test, with a combination of 90% probability, the 6% probability as well as the “cannot exclude with a less than 5% probability”, may reach 92% concordance with pathological diagnosis. It has the highest prediction in differentiation of 2-3 primaries, especially when one primary involves pancreas. However, the concordance between the clinical diagnosis and the diagnosis rendered by the ID test major prediction is not optimal, and will need further improvement.[Table: see text]
ANTICIPATE: A phase I/II, open-label, multicenter study to evaluate the safety and efficacy of oral APL-1202 in combination with tislelizumab compared to tislelizumab alone as neoadjuvant therapy (NAC) in patients with muscle invasive bladder cancer (MIBC).
Authors: Matt D. Galsky, John P. Sfakianos, Ding-Wei Ye, Mingming Zhang
Journal: Journal of Clinical Oncology (2022)

TPS4613 Background: Standard treatment for muscle invasive bladder cancer (MIBC) is radical cystectomy (RC) and administration of NAC in patients who are eligible to receive cisplatin. Approximately 50% of patients are ineligible to receive cisplatin as a result of pre-existing contraindications, and some refuse to receive any chemotherapy due to concerns of toxicities. Immune checkpoint inhibitors (ICIs) have been shown to be highly active in metastatic urothelial cancer. APL-1202 (nitroxoline) is a reversible and orally available MetAP2 inhibitor with anti-angiogenic and anti-tumor activities. Synergistic effects of APL-1202 and ICIs have been shown in model systems of bladder cancer. It is hypothesized that APL-1202 in combination with tislelizumab, a humanized IgG4 anti-PD-1 MAb, may be an effective neoadjuvant therapy in MIBC. This trial will evaluate the safety, efficacy, and pharmacodynamic effects of APL-1202 in combination with tislelizumab as neoadjuvant therapy for patients with MIBC who are cisplatin ineligible or refuse cisplatin-based chemotherapy. Methods: ANTICIPATE is an open-label, multi-center clinical trial enrolling 79 patients in two phases: Phase Ⅰ and Phase Ⅱ. Phase I is a dose escalation study to determine MTD (maximum tolerated dose) and/or RP2D. Phase II is an expanded proof-of-concept study to evaluate the safety and efficacy of APL-1202 in combination with tislelizumab compared to tislelizumab alone as neoadjuvant therapy for MIBC as measured by pathological complete response (pCR). Phase Ⅰ and Phase Ⅱ both are divided into 3 periods: screening period of 4 weeks, neoadjuvant therapy comprising 3 cycles (each 21 days) prior to radical cystectomy; and a follow-up period of up to 90 days after surgery. The phase Ⅰ will determine the RP2D of APL-1202 in combination with tislelizumab as neoadjuvant therapy for MIBC. Eligible patients have newly diagnosed MIBC and are cisplatin ineligible or refuse cisplatin-based NAC and are planned for RC. In phase Ⅰ, a standard 3+3 dose-escalation design will be used. On day 1 of each cycle, a single dose of 200 mg tislelizumab will be administered intravenously. The daily dose APL-1202 will be escalated in successive cohorts (375 mg à 750 mg à 1,125 mg). The DLT observation window for any dose level will be treatment cycle 1. There will be no intra-patient dose escalation. In phase II patients will be randomly assigned to group 1 (APL-1202 + tislelizumab) or group 2 (tislelizumab only), stratified by PD-L1 expression. The IND has been approved by FDA and NMPA, and the study execution is under preparation both in US and China. Clinical trial information: NCT04813107.
Effects of anxiety and depression on the quality of life of male cancer patients undergoing genetic investigation for hereditary cancer predisposition syndromes.
Authors: Francisca Fernanda Barbosa Oliveira, Paulo Goberlânio de Barros Silva, Flávio da Silveira Bitencourt, Rosane Oliveira Sant'Ana, Isabelle Joyce de Lima Silva-Fernandes, Maria Júlia Barbosa Bezerra, Maria Claudia dos Santos Luciano, Clarissa Gondim Picanço-Albuquerque, Thuany Pinto Rocha de Souza, Marcos Venício Alves Lima
Journal: Journal of Clinical Oncology (2022)

e22529 Background: Genetic tests have been increasingly requested to identify families at risk of hereditary cancer. In a family with a known mutation, the offspring of a carrier, whether male or female, have a 50% risk of inheriting the mutation. Most studies on the psychological implications associated with genetic testing have focused on women and few studies have focused on the male population. Methods: A total of 56 men with a personal history of cancer underwent screening for mutations in a panel of 31 genes associated with hereditary cancer. Assessment of quality of life (QoL) and levels of anxiety and depression was performed after patients received the genetic test result. For this, the HADS and WHOQOL-BREF scales were used. Wilcoxon, X², and Spearman correlation tests were used (SPSS v20.0 for Windows). Results: Of the 56 participants, 28.6% had a pathogenic mutation, 32.1% had a Variant of Undetermined Significance (VUS), and 39.3% had no mutation. The presence of the mutation was not associated with QoL (p = 0.967) or anxiety (p = 0.436) or depression (p = 0.945). Mean QoL was 77.95±7.38 (range = 50.00-95.20), mean anxiety was 5.14±2.62 (range = 1-14) and mean depression scores were 4.14±2.55 (range = 0-14). QoL was inversely correlated with levels of anxiety (p &lt; 0.001, r = -0.496) and depression (p &lt; 0.001, r = -0.494), parameters that were directly correlated (p = 0.037, r = 0.279). Most patients had QoL &gt; 80 (n = 38, 67.9%), and only 16 (28.6%) and 13 (23.2%) men had HAD scores &gt; 5. Conclusions: The result of carrying a mutation did not influence the quality of life and anxiety or depression levels in the male population evaluated. However, it was observed that levels of anxiety and depression can compromise the quality of life. The data from the present study reinforce the importance of considering the psychological aspects in the process of genetic investigation for hereditary cancer. In addition, it suggests that educational levels must be investigated to assess whether the low levels of anxiety and depression observed are associated with a low level of understanding of the clinical significance of carrying a pathogenic mutation.